N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis.

OBJECTIVES: To investigate the prevalence and temporal development of N-methyl-d-aspartate receptor (NMDAR) autoantibodies in relation to neurocognitive performance in patients with herpes simplex encephalitis (HSE). METHODS: This prospective observational study enrolled a total of 49 HSE patients within a randomized controlled trial of valacyclovir. Cerebrospinal fluid and serum samples were drawn in the initial stage of disease, after 2 to 3 weeks and after 3 months. Anti-NMDAR IgG was detected with HEK293 cells transfected with plasmids encoding the NMDA NR1 type glutamate receptor. A batch of neurocognitive tests, including the Mattis Dementia Rating Scale (MDRS), Glasgow Coma Scale (GCS), Reaction Level Scale (RLS85), Mini-Mental State Examination (MMSE) and National Institutes of Health (NIH) stroke scale, was performed during 24 months' follow-up. RESULTS: Anti-NMDAR IgG was detected in 12 of 49 participants. None were antibody positive in the initial stage of disease. In ten of 12 positive cases, specific antibodies were detectable only after 3 months. Notably, the development of NMDAR autoantibodies was associated with significantly impaired recovery of neurocognitive performance. After 24 months' follow-up, the median increase in MDRS total score was 1.5 vs. 10 points in antibody-positive and -negative participants (p=0.018). CONCLUSIONS: Anti-NMDAR autoimmunity is a common complication to HSE that develops within 3 months after onset of disease. The association to impaired neurocognitive recovery could have therapeutical implications, as central nervous system autoimmunity is potentially responsive to immunotherapy.

Medical intelligence in Sweden. Vitamin B12: oral compared with parenteral?

BACKGROUND: Sweden is the only country in which oral high dose vitamin B12 has gained widespread use in the treatment of deficiency states. OBJECTIVE: The aim of the study was to describe prescribing patterns and sales statistics of vitamin B12 tablets and injections in Sweden 1990-2000.Design, setting, and sources: Official statistics of cobalamin prescriptions and sales were used. RESULTS: The use of vitamin B12 increased in Sweden 1990-2000, mainly because of an increase in the use of oral high dose vitamin B12 therapy. The experience, in statistical terms a "total investigation", comprised 1,000,000 patient years for tablets and 750,000 patient years for injections. During 2000, 13% of residents aged 70 and over were treated with vitamin B12, two of three with the tablet preparation. Most patients in Sweden requiring vitamin B12 therapy have transferred from parenteral to oral high dose vitamin B12 since 1964, when the oral preparation was introduced. CONCLUSION: The findings suggest that many patients in other post-industrial societies may also be suitable for oral vitamin B12 treatment.

Thermodynamic characterization of the dimerization equilibrium of an asymmetric dye by spectral titration and chemometric analysis.

The monomer-dimer equilibrium of an asymmetric cyanine dye has been investigated by means of UV-Vis spectroscopy. The data have been processed by a recently developed chemometric method for quantitative analysis of undefined mixtures, that is based on simultaneous resolution of the overlapping bands in the whole set of absorption. In this work the dimerization constant of 1-carboxydecyl-4-{3-[3-methyl-3H-benzothiazol-2-ylidene]-propenyl}-quinolinium (TO-3) has been determined by studying the dependence of absorption spectrum on temperature in the range 25-72.5 degrees C at different total concentrations of dye (8.5x10(-6) to 2.87x10(-5)M). Utilizing the van't Hoff relation, which describes the dependence of the equilibrium constant on temperature, as constraint we determine the spectral responses of the monomer and dimer species as well as the enthalpy and entropy of the dimerization equilibrium.

["Target groups 1-3" must be granted priority access to health care services. Health care needs of somatically and mentally disabled persons in Robetsfors]. / "Personkrets 1-3" måste prioriteras inom vården. Vårdbehov hos somatiskt och psykiskt funktionshindrade i Robertsfors.

People with serious functional disabilities do not always call attention to their needs for care, and are therefore a vulnerable group in our society. In Sweden, The Act Concerning Support and Service for Persons with Certain Functional Impairments (LSS) is intended to provide for them. Our research found that people with serious physical or psychiatric disability suffer more often from intercurrent disease and have more problems with their eyesight, hearing and dental health than do other individuals. The responsibility for their respective health care needs must be clarified, so that the group is given priority access to the health care system and services for rehabilitation.

Vitamin B12 in primary health care and geriatrics--attitudes, knowledge and competence.

OBJECTIVES: The objective of the study was to test attitudes, knowledge and competence of Swedish general practitioners and geriatricians concerning B12-associated problems in 1998. METHODS: Postal questionnaires were sent to a random sample of 485 GPs and a total sample of 613 geriatricians. The response rates were 70% in the GP group and 69% in the geriatrician group. The questionnaire contained 24 statements to be evaluated by a visuo-analogue scale. RESULTS: There were small numerical differences between the two physician groups. The geriatricians were more aware of risk groups for B12 deficiency. GPs were less categorical concerning low hit rate in the laboratory testing of clinical conclusions. There were statistical differences in both directions for statements on pitfalls in laboratory diagnostics. GPs were somewhat less prone to give risk groups prophylactic B12 therapy. CONCLUSIONS: GPs and geriatricians appeared to be familiar with the current debate on B12-associated problems, suggesting that health care quality will be unaffected by patient transfer from hospital care to primary health care.

Shifts in B12 opinions in primary health care of Sweden.

AIMS: The diagnosis and management of vitamin B12 deficiency varies between countries and within countries. The aim of the study was to map current attitudes and values behind clinical decision-making in Swedish primary health care, which has a unique B12 tradition: two patients out of three are treated with oral high-dose cyanocobalamin. Most patients with B12-associated problems are managed in primary health care by general practitioners (GPs). METHODS: The study was designed to elucidate possible opinion shifts among GPs during the period 1996-1998. GPs (n=499), stratified and randomized, received a questionnaire with 24 statements on B12-associated clinical and laboratory problems, to be evaluated by a visuo-analogue scale. RESULTS: The majority of GPs in primary health care in Sweden accepted homocysteine and methylmalonic acid (MMA) as markers for functional deficiency of vitamin B12. The evaluation of classical markers of B12 deficiency was wary and balanced. There was a consensus of the need for B12 therapy to risk groups such as patients with atrophic gastritis or previous gastric surgery. The answers also appeared to reflect an improvement of professional knowledge and competence concerning B12-associated problems among Swedish GPs between 1996 and 1998. CONCLUSIONS: The overriding conclusion was that B12-associated opinions of Swedish GPs were stable within the period studied, with marginal improvements of knowledge and competence.

Free-probe fluorescence of light-up probes.

The fluorescence enhancement of light-up probes (thiazole orange (TO) conjugated peptide nucleic acids (PNAs)) upon hybridization to target nucleic acid depends on the probe sequence, mainly due to large variations in free-probe fluorescence. Here we study three probes where the fluorescence in free state varies more than 50-fold. We find that this variation is due to a fraction that has TO intramolecularly "back-bound" to the PNA bases. The intramolecular affinity constant for this unimolecular interaction was determined by temperature titrations using absorption spectroscopy, and the fluorescence quantum yields of the probes in back-bound conformation were calculated. The molar ratio of probes in back-bound conformation was 0.70-0.96 at 30 degrees C and 0.40-0.73 at 60 degrees C, and the fluorescence quantum yield in back-bound conformation varied between 0.0020 and 0.077 at 30 degrees C, and 0.00065-0.029 at 60 degrees C. These data show that the variation in free-probe fluorescence depends mainly on the fluorescence quantum yield of the probe in back-bound conformation and to a much lesser extent on the tendency of the probe to adopt the back-bound conformation. With increasing temperature the free-probe fluorescence decreases owing to both reduced degree of back-binding and a decrease of the fluorescence quantum yield in back-bound conformation.

[Experiences from the county of Norrbotten: screening of hearing at the age of four crucial for detecting mild hearing impairment]. / Erfarenheter från Norrbottens län: fyraårskontrollen av hörseln viktig för att hitta lätta hörselskador.

Since the eighties the formerly well established hearing screening performed at the age of four has been debated, partly for economic reasons. One quarter of Sweden's counties have since then abolished it. But how many children do we detect by this screening? What significance does it have for a child that those around it are aware of a mild hearing impairment? In Norrbotten, in all, we found 123 children born 1989-1992 with a hearing impairment. The prevalence was 7.9 per thousand. 30 percent of the children were detected at the 4-years hearing screening, and of these 0.9/1,000 had a hearing impairment that was bilateral, 1.0/1,000 unilateral and 0.5/1,000 impairment only in the high frequencies. Also children with mild bilateral or unilateral hearing impairment can experience difficulties in school and among friends, especially in noisy surroundings, and benefit by knowing early about their hearing impairment.

Rapid and specific detection of PCR products using light-up probes.

Newly developed light-up probes offer an attractive tool for PCR product detection. The light-up probe, which consists of a thiazole orange derivative linked to a peptide nucleic acid oligomer, hybridizes specifically to complementary nucleic acids. Upon hybridization the thiazole orange moiety interacts with the nucleic acid bases and the probe becomes brightly fluorescent. This eliminates the need to separate bound from unbound probes and reduces the risk of cross contamination during sample handling. We demonstrate here the applicability of light-up probes in two different PCR assays, one directed towards the human beta-actin gene and the other towards the invA gene of Salmonella. The probes do not interfere with the PCR reaction and can either be included in the sample mixture or added after completed amplification. The specificity of the probe is found to be excellent: a single-base mismatch in the target sequence is sufficient to prevent probe binding as indicated by the lack of fluorescence increase. Furthermore, a clear correlation is found between the intensity of gel bands and the measured probe fluorescence in solution, which suggests that the amount of PCR products can be quantified using light-up probes.

Light-up probes: thiazole orange-conjugated peptide nucleic acid for detection of target nucleic acid in homogeneous solution.

We have constructed light-up probes for nucleic acid detection. The light-up probe is a peptide nucleic acid (PNA) oligonucleotide to which the asymmetric cyanine dye thiazole orange (TO) is tethered. It combines the excellent hybridization properties of PNA and the large fluorescence enhancement of TO upon binding to DNA. When the PNA hybridizes to target DNA, the dye binds and becomes fluorescent. Free probes have low fluorescence, which may increase almost 50-fold upon hybridization to complementary nucleic acid. This makes the light-up probes particularly suitable for homogeneous hybridization assays, where separation of the bound and free probe is not necessary. We find that the fluorescence enhancement upon hybridization varies among different probes, which is mainly due to variations in free probe fluorescence. For eight probes studied the fluorescence quantum yield at 25 degrees C in the unbound state ranged from 0.0015 to 0.08 and seemed to depend mainly on the PNA sequence. The binding of the light-up probes to target DNA is highly sequence specific and a single mismatch in a 10-mer target sequence was readily identified.

Sense of coherence in different stages of health and disease in northern Sweden--gender and psychosocial differences.

OBJECTIVE: To investigate "Sense of Coherence" (SOC) and its relation to perceived health, different stages of disease, and different psychosocial factors in a population-based study. DESIGN: Postal survey of a population-based sample, the MONICA study (1994). SETTING: Norrbotten and Västerbotten, the two northernmost counties in Sweden, with a total population of 510000 inhabitants. SUBJECTS: 837 men and 882 women in three mutually-exclusive groups: stomach trouble of many years' standing, identified disease (stroke, cardiac infarction, diabetes, anti-hypertension treatment) and no reported disease. MAIN OUTCOME MEASURES: SOC scores in relation to sociodemographic variables and perceived health. RESULTS: We found a relationship between low SOC scores and poor perceived health, low social support and low emotional support on a population level. When comparing persons with stomach trouble with those without disease, or with established diseases, we found similar relationships between low mean SOC scores in all strata for both women and men. "Perceived health", however, was only significantly correlated for women, and women had an overall stronger relationship. CONCLUSIONS: In a study in northern Sweden, female patients with stomach trouble comprise a vulnerable group. The concept of SOC introduces a new dimension for perceiving health and disease. In clinical practice, care providers can identify and elaborate on the relationship between SOC scores and sociodemographic data.

The impact of patients' influence on recovery in a group of patients with dyspepsia.

BACKGROUND: The approach to health and disease can either be salutogenic (origins of health) or pathogenic (disease causing), which thus makes recovery a concept featuring several different angles. Antonovsky, with his concept of salutogenesis, tried to reach a more complete understanding of its favourable effects on health. OBJECTIVE: We aimed to investigate, understand and learn from the experiences of a small group of patients about factors leading to recovery. METHODS: A qualitative approach was used to explore patient experiences. One semi-structured interview was conducted by one of the authors (BN) with each of the 18 patients suffering from dyspepsia who had been investigated by means of gastroscopy at a university hospital clinic 12-15 years previously. The interviews were recorded either in written notes composed directly after the interviews or tape-recorded and subsequently transcribed. A modified form of grounded theory according to Strauss-Corbin was used to analyse the data. RESULTS: A pattern featuring five types of patients' influence on their lives was discerned, ranging from "a sense of no possibility of having an influence on existence/life" to "having influence". Strategies used by patients to maintain health could be categorized into four types: "extremists", "oscillators", "leapers" and "full-scalers". CONCLUSIONS: Listening to patients who had experiences with dyspepsia brought patient influence on their own lives and on the care process into focus. We consider that there might be a link between patients having an influence on their lives and their being healthy today. In clinical practice, patient recovery and health promotion could gain from a perspective where patient influence is treated with esteem and emphasized in the consultation. In the future, research design could benefit from taking patient influence on the care process into consideration. However, no causal linkage between patient influence and patient outcome was established in this study. In order to do that, studies with quantitative design should be undertaken in the future.

Megestrol acetate in advanced, progressive, hormone-insensitive cancer. Effects on the quality of life: a placebo-controlled, randomised, multicentre trial.

A randomised double-blind placebo-controlled multicentre trial was performed to investigate the effects of megestrol acetate (MA) on the quality of life (QoL), appetite, weight and survival of patients with advanced, incurable, hormone-insensitive cancer. QoL was assessed at the start of treatment and at 4, 8 and 12 weeks, using the EORTC-QLQ-C30 instrument. 255 patients were randomised to 320 mg of MA daily or placebo for 12 weeks. 244 patients were assessable at baseline, 190 at 4 weeks (placebo 94; MA 96), 150 at 8 weeks (placebo 69; MA 81) and 112 at 12 weeks (placebo 55; MA 57). A beneficial effect of MA on appetite loss was observed at week 4 (P < 0.0001) and possibly at week 8 (P = 0.058). Further weight loss during treatment was significant only in the placebo group. In the first 8 weeks, changes in mean global QoL were small and similar in both groups. By 12 weeks the decrease in mean global QoL was more pronounced in the MA group (P = 0.028), which was related to a deterioration in physical function, while psychosocial function was not affected. Survival was not affected by MA, and side-effects were mild. The results show that MA has a beneficial effect on appetite and that it may retard weight loss with no adverse impact on survival and with mild toxicity. However, MA does not appear to improve global QoL as measured by the EORTC QLQ-C30.

Women with false positive screening mammograms: how do they cope?

OBJECTIVES: To assess the long term psychological impact on women who were recalled for further investigation after mammography screening and to find any factors that might predict coping ability in order to identify those subjects who require additional support at an earlier stage. SETTING: Counties of Västerbotten and Västernorrland, Sweden. METHODS: A prospective design was used in which 252 recalled women completed questionnaires twice--once within a week of having received the all-clear and again at follow up six months later. A group of 1104 randomly selected, screen negative women were followed up in the same way for comparison. The questionnaire included the Psychological Consequences Questionnaire (PCQ) and basic sociodemographic data. The main outcome measure was the total score on the PCQ at six months. RESULTS: Of the 252 women, 235 (93%) completed both questionnaires. In the control group, 987 (89.4%) women responded. Six months after the all-clear, recalled women were still significantly more anxious (p < 0.001) than those who had been screened but not recalled. The strongest predictor of psychological distress at six months was the PCQ score at the first measurement. Other predictors were a low level of education, living in high density urban areas, and having only one child or no children at all. Widows appeared to cope better than other women. CONCLUSIONS: It is possible to define a group of women with false positive results who are already at risk of coping less effectively at the time of recall. Offering these women counselling or other types of support should be considered.

Cross-comparison of two quality of life instruments used in a randomized study of combination chemotherapy in advanced breast cancer.

Twenty-six patients from a randomized study of combination chemotherapy in advanced breast cancer were included in a cross-comparison between two quality of life instruments: a categorical linear analogue scale (C-LASA) based on the instrument of Priestman and Baum and a Swedish instrument developed by Glimelius et al. Quality of life was assessed on day 1 and day 10 of each chemotherapy cycle and the instruments were compared using correlation and kappa analysis. For the physical dimension, the mean correlation coefficient on day 1 was 0.89 and the kappa coefficient was 0.62; and on day 10 the correlation coefficient was 0.83 and the kappa coefficient 0.62. For the emotional dimension the correlation and kappa coefficients were 0.89 and 0.71 and 0.89 and 0.61 on days 1 and 10, respectively. The corresponding values for the global dimension were 0.76 and 0.56 and 0.80 and 0.57 on days 1 and 10, respectively. A correlation was also demonstrated over time. The instruments gave similar measurements of quality of life for chemotherapy-treated patients with advanced breast cancer, but the feasibility of the C-LASA instrument was better.

The meanings of pain: an exploration of women's descriptions of symptoms.

A grounded theory study with repeated semi-structured interviews was conducted to explore the meaning of the illness experiences of women patients, impaired by biomedically undefined musculoskeletal pain. Twenty female patients were recruited at an urban primary health care centre in northern Sweden, where two of the researchers work as family physicians. In this paper we focus on considerations of patient pain and analyze the findings from aspects linking together body, gender, and society. Four categories of symptom description were identified: bodily presentations, explanatory models, consequences of pain for the patient's activities, and consequences for her self-perception. The bodily symptoms signaled loss of control. The explanatory models consisted of physical damage and strain injuries, but were also psychological and self-blaming. The consequences of pain were described as negative consequences for the women's everyday life that challenged their self-perception as women. The participants' search and need for legitimization of their illness experiences, and the expectations placed on doctors as legitimizing agents was evident. To achieve the desired shared understanding in consultations, doctors must be aware of and consider not only physical signs and symptoms, but also the patients' gendered concerns and psycho-social circumstances.

Shifting the distribution of risk: results of a community intervention in a Swedish programme for the prevention of cardiovascular disease.

STUDY OBJECTIVE: To examine the impact of a systematic risk factor screening and counselling carried out by family physicians and family nurses within the larger framework of a community intervention programme for the prevention of cardiovascular disease (CVD). DESIGN: Quasi-experimental study comparing trends in an intervention area with those in a reference area. SETTING: A Northern Sweden municipality (5500 inhabitants) constituted the intervention area while the Northern Sweden region (510,000 inhabitants) served as the reference area. PARTICIPANTS: All 30, 40, 50, and 60 year old inhabitants were invited each year from 1985 to 1992. Among 2046 eligible 1893 participated (92.5%), which formed eight independent cross sections. One cross section, 1986, was re-surveyed forming a panel. MAIN RESULTS: In the cross sections, mean total cholesterol was reduced from 7.09 to 6.27 mmol/l for men (p < 0.001) and from 7.13 to 5.89 mmol/l for women (p < 0.001) and mean systolic blood pressure from 132.2 to 123.7 mm Hg for men (p < 0.05) and from 129.2 to 122.0 mm Hg for women (p < 0.001) during the eight years. Body mass index (BMI) increased from 25.6 to 26.2 for men (p < 0.05) and from 25.0 to 25.5 for women (NS). A corresponding reduction in cholesterol and blood pressure (for women) occurred in the panel, while BMI was unchanged. The risk for CVD, using the Framingham equation, was estimated to be reduced overall by 19% (p = 0.0021) when comparing early cross sections (1985/86) with the later cross sections (1990/91). CONCLUSIONS: It was concluded that a long term community based CVD prevention programme that combines population and individual strategies can substantially promote a health shift in CVD risk in a high risk rural population. The individual attention and evaluation provided by the health provider survey seem to accelerate, but not increase the amount of, risk reduction.

Prevalence of sexualized violence among women. A population-based study in a primary healthcare district.

In order to estimate the prevalence of sexual and physical abuse, postal questionnaires were sent to a random sample of 251 adult women in a primary care district. Three yes/no-questions were asked on these topics, and a fourth inquired into effects on health. Space was left for open-ended answers in which yes-responders were invited to write about their experiences. A total of 175 women (70%) answered, and 25 (14%) of these reported abuse. Nine (5%) had experienced women battering. Thirteen (7.5%) reported sexual abuse as an adult, and 12 (7%) as a child. Many told their stories. Methodological shortcomings in this study might explain why the rates are somewhat lower than in other investigations. However, our figures verified that abuse of women is a common social phenomenon. They also confirmed abuse as a major health problem for women. One-third of respondents explicitly reported effects on health. Others, though negating such effects, described them in written narratives. In order to study this contradiction, in-depth interviews with abused women are recommended.

Reduction of selection bias in primary prevention of cardiovascular disease through involvement of primary health care.

OBJECTIVE: To examine selection bias in social and health factors in a community intervention programme for the prevention of cardiovascular disease by comparing programme data with both census data and a random sample of the same population. DESIGN: Cross sectional studies. SETTING: All 35 primary health care centres in Västerbotten County, Sweden. SUBJECTS: 24,870 individuals who during 1992 and 1993 became 30, 40, 50 or 60 years of age. MAIN OUTCOME MEASURES: Total income, socio-economic group, employment, education, body mass index (BMI), total cholesterol, systolic and diastolic blood pressure, and daily smoking. RESULTS: The differences in social characteristics between participants and non-participants were marginal, indicating that the social selection bias was small. However, unemployment, low income, and younger age tended to be associated with somewhat lower preference to participate. The overall pattern of health status, as measured by risk factors, was similar rather than dissimilar. While the participants in the intervention health survey had lower mean total cholesterol, their blood pressure was generally higher compared with the reference random sample. CONCLUSIONS: The primary health care system in Sweden might serve as a useful base for educational health counselling, at least within a community intervention programme, for all levels of society.